The Interaction Effect of 27-Hydroxycholesterol Metabolism Disorder and CYP27A1 Single Nucleotide Polymorphisms in Mild Cognitive Impairment: Evidence from a Case-Control Study.

Abstract

SCOPE:

The aim of the study is to investigate the relationship between 27-hydroxycholesterol (27-OHC), 27-hydroxylase (CYP27A1) polymorphisms, and Alzheimer's disease (AD).

METHODS AND RESULTS:

A case-control study based on EMCOA study includes 220 healthy cognition and mild cognitive impairment (MCI) subjects respectively, matched by sex, age, and education. The level of 27-OHC and its related metabolites are examined by high performance liquid chromatography-mass spectrometry (HPLC-MS). The results show that 27-OHC level is positively associated with risk of MCI (p < 0.001), negatively associated with specific domain of cognitive function. Serum 27-OHC is positively associated with 7a-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA) in cognitive healthy subjects, while positively associated with 3β-hydroxy-5-cholestenoic acid (27-CA) in MCI subjects (p < 0.001). CYP27A1 and Apolipoprotein E (ApoE) single nucleotide polymorphisms (SNPs) genotyping are determined. The global cognitive function is significant higher in Del-carrier of rs10713583, compared with AA genotype (p = 0.007). Stroop Color-Word Test Interference Trial (SCWT-IT) is significant higher in G-carrier genotype (p = 0.042), compared with TT genotype in rs12614206.

CONCLUSIONS:

The results show that 27-OHC metabolic disorder is associated with MCI and multi-domain cognitive function. CYP27A1 SNPs is correlated to cognitive function, while the interaction between 27-OHC and CYP27A1 SNPs need further study.

• Authors: Lijing Wang, Huiyan Yu, Ling Hao, Mengwei Ju, Wenjing Feng, Rong Xiao
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 67 Issue 10 Pg. e2200576 (05 2023) ISSN: 1613-4133 [Electronic] Germany
• PMID: 36811281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 Wiley-VCH GmbH.

Chemical References

• 27-hydroxycholesterol
• Hydroxycholesterols
• Cytochrome P-450 Enzyme System
• CYP27A1 protein, human
• Cholestanetriol 26-Monooxygenase

Topics

• Humans
• Polymorphism, Single Nucleotide
• Case-Control Studies
• Cognitive Dysfunction (genetics)
• Hydroxycholesterols (metabolism)
• Alzheimer Disease (genetics)
• Cytochrome P-450 Enzyme System (genetics)
• Cholestanetriol 26-Monooxygenase (genetics)